Optimized shortened peptide that binds to acetylcholine receptor, and use thereof

Abstract

The present disclosure relates to an optimized shortened peptide that binds to an acetylcholine receptor, and a use thereof. It is expected that it is possible to develop a cosmetic composition for alleviating wrinkles, pharmaceuticals for preventing or treating acetylcholine receptor-related diseases, and health functional foods for improvement of the acetylcholine receptor-related diseases, by using the optimized shortened peptide of the present disclosure, which is shorter than conventional acetylcholine receptor inhibitory peptides but has a high acetylcholine receptor binding force and an acetylcholine receptor inhibitory effect.

1 . An acetylcholine receptor-binding peptide, comprising the amino acid sequence represented by the following Chemical Formula 1:
   (R/K)XXX(R/K)  [Chemical Formula 1]
   
       (wherein R/K is arginine or lysine, X is any amino acid). 
     
     
         2 . An acetylcholine receptor-binding peptide, comprising the amino acid sequence represented by the following Chemical Formula 1-1:
   (R/K)XYZ(R/K)  [Chemical Formula 1-1]
   
       (wherein R/K represents either arginine or lysine, and XYZ represents a sequence of any three consecutive amino acids, with X being an amino acid selected from R, Q, G, V, L, S, and W, Y being an amino acid selected from R, Q, L, I, F, V, and Y, and Z being an amino acid selected from R, S, L, C, Y, Q, and T). 
     
     
         3 . The acetylcholine receptor-binding peptide of  claim 2 , wherein the peptide comprises an amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID NOS: 1 to 600. 
     
     
         4 . An acetylcholine receptor-binding peptide, comprising the amino acid sequence represented by the following Chemical Formula 1-2:
   XRRQRR  [Chemical Formula 1-2]
   
       (wherein R represents arginine, Q represents glutamine, and X represents any one amino acid). 
     
     
         5 . The acetylcholine receptor-binding peptide of  claim 4 , wherein the peptide comprises an amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID NOS: 3601 to 3620. 
     
     
         6 . An acetylcholine receptor-binding peptide, comprising the amino acid sequence represented by the following Chemical Formula 1-3:
   RRQRRX  [Chemical Formula 1-3]
   
       (wherein R represents arginine, Q represents glutamine, and X represents any one amino acid). 
     
     
         7 . The acetylcholine receptor-binding peptide of  claim 6 , wherein the peptide comprises an amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID NOS: 3621 to 3640. 
     
     
         8 . An acetylcholine receptor-binding peptide, comprising the amino acid sequence represented by the following Chemical Formula 2:
   (R/K)(R/K)XXX(R/K)  [Chemical Formula 2]
   
       (wherein R/K represents either arginine or lysine, and X represents any one amino acid). 
     
     
         9 . An acetylcholine receptor-binding peptide, comprising the amino acid sequence represented by the following Chemical Formula 2-1:
   (R/K)(R/K)XYZ(R/K)  [Chemical Formula 2-1]
   
       (wherein R/K represents either arginine or lysine, XYZ represents a sequence of any three consecutive amino acids, with X being an amino acid selected from R, Q, G, V, L, S, and W, Y being an amino acid selected from R, Q, L, I, F, V, and Y, and Z being an amino acid selected from R, S, L, C, Y, Q, and T). 
     
     
         10 . The acetylcholine receptor-binding peptide of  claim 9 , wherein the peptide comprises an amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID NO: 1201 to 1800. 
     
     
         11 . An acetylcholine receptor-binding peptide, comprising the amino acid sequence represented by the following Chemical Formula 2-2:
   XRRGVRR  [Chemical Formula 2-2]
   
       (wherein R represents arginine, G represents glycine, V represents valine, and X represents any one amino acid). 
     
     
         12 . The acetylcholine receptor-binding peptide of  claim 11 , wherein the peptide comprises an amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID NOS: 3641 to 3660. 
     
     
         13 . An acetylcholine receptor-binding peptide, comprising the amino acid sequence represented by the following Chemical Formula 2-3:
   RRGVRRX  [Chemical Formula 2-3]
   
       (wherein R represents arginine, G represents glycine, V represents valine, and X represents any one amino acid). 
     
     
         14 . The acetylcholine receptor-binding peptide of  claim 13 , wherein the peptide comprises an amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID NOS: 3661 to 3680. 
     
     
         15 . An acetylcholine receptor-binding peptide, comprising the amino acid sequence represented by the following Chemical Formula 3:
   (R/K)XXX(R/K)(R/K)   
       (wherein R/K represents either arginine or lysine, and X represents any one amino acid). 
     
     
         16 . An acetylcholine receptor-binding peptide, comprising the amino acid sequence represented by the following Chemical Formula 3-1:
   (R/K)XYZ(R/K)(R/K)  [Chemical Formula 3-1]
   
       (wherein R/K represents either arginine or lysine, XYZ represents a sequence of any three consecutive amino acids, with X being an amino acid selected from R, Q, G, V, L, S, and W, Y being an amino acid selected from R, Q, L, I, F, V, and Y, and Z being an amino acid selected from R, S, L, C, Y, Q, and T). 
     
     
         17 . The acetylcholine receptor-binding peptide of  claim 16 , wherein the peptide comprises an amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID NOS: 2401 to 3000. 
     
     
         18 . The acetylcholine receptor-binding peptide of  claim 1 , wherein the peptide has a modification to the N-terminus or C-terminus thereof. 
     
     
         19 . The acetylcholine receptor-binding peptide of  claim 18 , the modification to the N-terminus or C-terminus is palmitoylation, acetylation, formylation, PEGylation, or conjugation with 2-mercaptoacetic acid, 3-mercaptopropionic acid, 6-mercaptohexanoic acid, pyroglutamic acid, succinimide acid, amide, cystramine, methyl ester, ethyl ester, benzyl ester, or a fatty acid, such as at least one selected from the group consisting of myristic acid, stearic acid, palmitic acid, cholesterol, 6-amino hexanoic acid, and 8-amino octanoic acid. 
     
     
         20 . A polynucleotide, coding for the peptide of  claim 1 . 
     
     
         21 . A composition, comprising the peptide of  claim 1 , and at least one selected from an adjuvant, an additive, or a pharmaceutically acceptable excipient. 
     
     
         22 . A method for prevention or treatment of an acetylcholine receptor hyperactivity-associated disease, comprising administering to a mammal in need thereof an effective amount of the peptide of  claim 1 . 
     
     
         23 . The method of  claim 22 , wherein the acetylcholine receptor hyperactivity-associated disease is at least one selected from the group consisting of cervical dystonia, limb dystonia, truncal dystonia, blepharospasm, spasticity, hemifacial spasm, strabismus, nystagmus, tics, chronic pain, chronic migraine, neurogenic bladder, detrusor-sphincter dyssynergia, achalasia cardia, hyperhidrosis, neuropathic pain, skin wrinkles, square jaw, and sialorrhea. 
     
     
         24 . A method for alleviation of an acetylcholine receptor hyperactivity-associated disease, comprising administering to a mammal in need thereof an effective amount of the peptide of  claim 1 . 
     
     
         25 . A medical device, comprising the composition of  claim 21 . 
     
     
         26 . A method for relief of skin wrinkles comprising administering to a mammal in need thereof an effective amount of the peptide of  claim 1 .